A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations.
- Conditions
- MelanomaNon-Small-Cell Lung CancerThyroid CancerGlioma
- Interventions
- Registration Number
- NCT05355701
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07799933) administered as a single agent and in combination with other study medicines (called binimetinib) in people with solid tumors.
This study is seeking participants who have an advanced solid tumor with a certain type of abnormal gene called "BRAF" and available treatments are no longer effective in controlling their cancer.
All participants in this study will receive PF-07799933. PF-07799933 comes as a tablet to take by mouth, 2 times a day. Depending on the part of the study, participants may also receive another study medicine:
* People with melanoma or other solid tumors may also receive binimetinib. Binimetinib comes as a tablet to take by mouth, 2 times a day.
* People with colorectal cancer may also receive cetuximab. Cetuximab will be given weekly (or every two weeks) in the clinic as a shot given in the vein or port (intravenous, IV).
Participants may receive the study medicines for about 2 years. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 156
- Diagnosis of advanced/metastatic solid tumor including primary brain tumor.
- Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid [DNA], or ctDNA).
- Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1 and Part 2).
- Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapies
- Brain metastasis larger than 4 cm
- Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
- For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination dose escalation (Part 2) cetuximab Participants will receive PF-07799933 in combination with binimetinib or cetuximab Monotherapy dose escalation (Part 1) PF-07799933 Participants will receive PF-07799933 Combination dose escalation (Part 2) binimetinib Participants will receive PF-07799933 in combination with binimetinib or cetuximab Dose expansion (Part 3) - Tumor and mutation specific Cohort 2 PF-07799933 Participants will receive PF-07799933 Dose expansion (Part 3) - Tumor and mutation specific Cohort 2 binimetinib Participants will receive PF-07799933 Combination dose escalation (Part 2) PF-07799933 Participants will receive PF-07799933 in combination with binimetinib or cetuximab Dose expansion (Part 3) - Tumor and mutation specific Cohort 1 PF-07799933 Participants will receive PF-07799933
- Primary Outcome Measures
Name Time Method RDE (Part 1 and Part 2) Cycle 1 (21 days) Recommended dose for expansion (RDE)
Number of participants with dose limiting toxicities (DLTs) (Part 1 and Part 2) Cycle 1 (21 days) DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with binimetinib or cetuximab
Dose dose modifications due to AEs (Part 1 and Part 2) Baseline to 2 years Incidence of dose modifications due to AEs
Number of participants with treatment-emergent adverse events (AEs) (Part 1 and Part 2) Baseline to 28 days after last dose of study medication AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Number of participants with clinically significant change from baseline in laboratory abnormalities (Part 1 and Part 2) Baseline to 28 days after last dose of study treatment Laboratory abnormalities as characterized by type, frequency, severity, and timing
Number of participants with clinically significant change from baseline in vital sign abnormalities (Part 1 and Part 2) Baseline to 28 days after last dose of study treatment Vital sign abnormalities as characterized by type, frequency, severity, and timing
Discontinuations due to AEs (Part 1 and Part 2) Baseline to 2 years Incidence of discontinuations due to AEs
MTD (Part 1 and Part 2) Cycle 1 (21 days) Maximum tolerated dose (MTD)
Overall response rate (ORR) (Part 3) Baseline to 2 years Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Dose interruptions due to AEs (Part 1 and Part 2) Baseline to 2 years Incidence of dose interruptions due to AEs
Number of participants with clinically significant physical exam abnormalities (Part 1 and Part 2) Baseline to 28 days after last dose of study treatment Physical exam abnormalities as as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2: ORR Baseline to 2 years ORR as assessed using the RECIST version 1.1.
Part 3: Disease Control Rate (DCR) Baseline to 2 years DCR
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, accumulation ratio (Rac) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Rac (AUCτ /AUCsd,τ)
Part 1 and Part 2: Duration of response Baseline to 2 years Duration of response
Part 1/2/3: PK parameters of PF-07799933, Single dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799933, Single dose, Cmax
Part 1/2/3: PK parameters of PF-07799933, Single dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799933, Single dose, Tmax
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUClast
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, maximum observed concentration (Cmax) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Cmax
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 24 hours (AUC24) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUC24
Part 1/2/3: PK parameters of PF-07799933, Single dose, terminal elimination half life (t½) Baseline to 2 years PK parameters of PF-07799933, Single dose, t½
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, time to maximum plasma concentration (Tmax) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Tmax
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, area under the plasma concentration-time curve over the dosing interval (AUCτ) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, AUCτ
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, CL/F Baseline to 2 years PK parameters of PF-07799933, Multiple dose, CL/F
Part 3: Number of participants with clinically significant change from baseline in vital sign abnormalities Baseline to 2 years Vital sign abnormalities as characterized by type, frequency, severity, and timing
Part 3: Dose dose modifications due to AEs Baseline to 2 years Incidence of dose modifications due to AEs
Part 3: Discontinuations due to AEs Baseline to 2 years Incidence of discontinuations due to AEs
Part 3: Time to event endpoints in each combination Baseline to 2 years Time to event endpoints in each combination
Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent oral clearance (CL/F) Baseline to 2 years PK parameters of PF-07799933, Single dose, CL/F
Part 1/2/3: PK parameters of PF-07799933, Single dose, apparent volume of distribution (Vz/F) Baseline to 2 years PK parameters of PF-07799933, Single dose, Vz/F
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, t1/2 Baseline to 2 years PK parameters of PF-07799933, Multiple dose, t1/2
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, trough plasma or serum concentration (Ctrough) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Ctrough
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, average plasma concentration (Cav) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Cav
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, peak-to-trough ratio (PTR) Baseline to 2 years PK parameters of PF-07799933, Multiple dose, PTR
Part 3: PK parameters of cytochrome P450 (CYP)3A4 probe substrate midazolam, Cmax Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, Cmax
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Tmax Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, Tmax
Part 1/2/3: Intracranial response Baseline to 2 years Intracranial response by RECIST version 1.1 (for brain metastases) \& Response Assessment in Neuro-Oncology (RANO) - for primary brain tumors).
Part 3: Number of participants with clinically significant change from baseline in laboratory abnormalities Baseline to 2 years Laboratory abnormalities as characterized by type, frequency, severity, and timing
Part 1/2/3: PK parameters of PF-07799933, Multiple dose, Vz/F Baseline to 2 years PK parameters of PF-07799933, Multiple dose, Vz/F
Part 3: TTR Baseline to 2 years Time to response (TTR)
Part 3: PFS Baseline to 2 years Progression-free survival (PFS)
Number of participants with clinically significant physical exam abnormalities (Part 3) Baseline to 28 days after last dose of study medication Physical exam abnormalities as as graded by NCI CTCAE version 5.0
Part 3: Number of participants with treatment-emergent adverse events (AEs) Baseline to 2 years AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
Part 3: Dose interruptions due to AEs Baseline to 2 years Incidence of dose interruptions due to AEs
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under plasma concentration-time curve over 48 hours (AUC48) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUC48
Part 1/2/3: PK parameters of PF-07799933, Single dose, area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) Baseline to 2 years PK parameters of PF-07799933, Single dose, AUCinf
Part 3: PK parameters of CYP3A4 probe substrate midazolam, Vz/F Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, Vz/F
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUClast Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, AUClast
Part 3: PK parameters of CYP3A4 probe substrate midazolam, t½ Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, t½
Part 3: PK parameters of CYP3A4 probe substrate midazolam, AUCinf Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, AUCinf
Part 3: PK parameters of CYP3A4 probe substrate midazolam, CL/F Baseline to 2 years PK parameters of CYP3A4 probe substrate midazolam, CL/F
Part 3: DOR Baseline to 2 years Duration of response (DOR)
Part 3: OS Baseline to 2 years Overall survival (OS)
Trial Locations
- Locations (36)
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
DFCI Chestnut Hill
🇺🇸Newton, Massachusetts, United States
Clinical and Translational Research Center (CTRC)
🇺🇸Aurora, Colorado, United States
Henry Ford Medical Center - Columbus
🇺🇸Novi, Michigan, United States
MSK David H. Koch Center for Cancer Care
🇺🇸New York, New York, United States
Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
🇺🇸Cleveland, Ohio, United States
UCHealth Sue Anschutz-Rodgers Eye Center
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
University of Miami Hospital and Clinics, Sylvester Cancer Center
🇺🇸Miami, Florida, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Providence Cancer Institute Franz Clinic
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute - Pharmacy
🇺🇸Nashville, Tennessee, United States
Brigitte Harris Cancer Pavilion
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
MSK Monmouth
🇺🇸Middletown, New Jersey, United States
TriStar Bone Marrow Transplant
🇺🇸Nashville, Tennessee, United States
Memorial Sloan Kettering Cancer Center 53rd street
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
TriStar Centennial Medical center
🇺🇸Nashville, Tennessee, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States
TriStar Centennial Medical Center - Cell Processing Lab
🇺🇸Nashville, Tennessee, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Sheba Medical Center
🇮🇱Ramat Gan, Hamerkaz, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Hamerkaz, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Yerushalayim, Israel
Rambam Health Care Campus
🇮🇱Haifa, Ḥeifā, Israel